ANTIHYPERTENSIVE TREATMENT WITH A VASODILATING BETA-BLOCKER, CARVEDILOL, IN CHRONIC-HEMODIALYSIS PATIENTS

Carvedilol is an antihypertensive agent which displays unselective bet a-blocking, alpha 1-blocking and antioxidant properties. It is primari ly metabolized by the liver and excreted via the biliary system. The c ompound is highly lipophilic and strongly bound to plasma proteins. Co nsequently, there is no elimination during hemodialysis. The efficacy, safety and pharmacokinetic profil of carvedilol titrated to effect we re investigated in an open clinical trial in 15 long-term hemodialysis patients with arterial hypertension over a period of 12 weeks. The dr ug was administered only on days without dialysis. After a wash-out ph ase of one week, carvedilol was started in a dose of 12.5 mg per day A ll 15 patients were titrated according to the antihypertensive effect to a daily dose of 25 mg of carvedilol. Carvedilol was effective in lo wering blood pressure in hemodialysis patients (RR systolic: 170 +/- 1 1 vs. 144 +/- 9 mmHg; RR diastolic: 98 +/- 10 vs. 85 +/- 10 mmHg). The pharmacokinetic parameters of carvedilol and its active metabolite M2 , assessed in 12 of the 15 patients, were not influenced by the lack o f renal function or intermittend haemodialysis. In particular, there w as no accumulation of carvedilol or its metabolite M2. In terms of sid e effects, three patients had to be withdrawn from the trial, because of hypoglycemia (n = 1), insufficient blood pressure control (n = 1) a nd prolonged hypotension (n = 1). Taken together, these results indica te that carvedilol is a safe and efficacious antihypertensive agent wh ich can be used in patients maintained by maintenance dialysis treatme nt.